Bacterial infection-related glomerulonephritis in patients with diabetes

Abstract

Aim: Diabetic patients are prone to infections, thus making them a unique cohort at risk of developing bacterial infection-related glomerulonephritis (IRGN).

Methods: In total, 1693 adult diabetic patients underwent kidney biopsy between 2005 and 2021 at our tertiary care hospital in South India. Of these, 121 consecutive cases which met criteria of bacterial IRGN were included in this study.

Results: The mean age of the cohort was 53.1 ± 10.1 years and 83/121 (68.5%) were males. Majority (98.3%) had type 2 diabetes for a median duration of 6 (IQR, 2-12) years. The most common sites of infection were skin (47/121, 38.8%) and urinary tract (15/121, 12.4%). Fifty percent (58/121) of patients had underlying advanced diabetic kidney disease (DKD). Isolated C3 deposits (without immunoglobulin) occurred in 66/121 (54.5%) patients predominantly in advanced DKD patients. IgA-dominant glomerulonephritis occurred in only 9/121 (7.4%) patients. Short-course oral steroid was given to 86/121 (71.1%) patients. Steroid related dysglycemia and immunosuppression related infections occurred in 9/61 (14.8%) and 16/61 (26.2%) patients respectively. Of the 90 patients with follow up details >3 months, 46 (51.1%) progressed to kidney failure over a median period of 0.5 (IQR, 0-7.2) months. Patients diagnosed in the latter half of our study period (2013-2021) were older, less commonly presented with fever, had more pronounced hypocomplementemia and severe renal histology predominantly with a 'starry sky' immunofluorescence pattern.

Conclusion: Superimposed bacterial IRGN on underlying DKD is associated with poor renal outcomes. Use of short course steroid was associated with significant toxicity.

Keywords: diabetic nephropathy; fibrosis; glomerulonephritis; immunopathology; infectious diseases; renal failure.

Figure 1

Flowchart of GRACE-IRGN Cohort. DKD, diabetic kidney disease; GRACE-IRGN, glomerular research and clinical experiments-Infection-related glomerulonephritis in diabetics.

Figure 2. Profile of bacterial infection-related glomerulonephritis in diabetics.

(A) Indications for kidney biopsy. (B) Classification based on severity of diabetic kidney disease. (C) Common sites of infection in para and post-infectious glomerulonephritis. (D) Classification based on period of IRGN diagnosis. ATI, acute tubular injury; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; IF, immunofluorescence; IFTA, interstitial fibrosis and tubular atrophy; RRT, renal replacement therapy.

Figure 3. Histopathology of bacterial infection-related glomerulonephritis in diabetics.

(A) Glomeruli with changes of diabetic glomerulopathy demonstrated by pronounced mesangial expansion with Kimmelsteil Wilson nodules, along with concomitant global endocapillary hypercellularity and neutrophilic exudation (Haematoxylin and Eosin stain, original magnification ×200). (B) Immunofluorescence microscopy demonstrating granular ‘starry sky’ pattern of C3 along glomerular mesangium and segmental capillary walls (original magnification ×200). (C) Immunofluorescence microscopy demonstrating confluent ‘garland’ pattern of staining of IgG along glomerular capillary walls (original magnification ×200). (D) Glomerulus displaying prominent large discrete subepithelial ‘hump’ like capillary wall electron dense deposits (arrowheads). Few mesangial and subendothelial electron dense deposits are also noted. Overlying podocytes show severe foot process effacement with cytoplasmic microvillous transformation (Transmission EM; original magnification, ×4200).

Figure 4

Predictors of kidney failure by Kaplan–Meier survival analysis. CKD-EPI, chronic kidney disease epidemiology collaboration; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; GN, glomerulonephritis; IFTA, interstitial fibrosis and tubular atrophy.